Claudia Pizzi

Desferioxamine increases iron depletion and apoptosis induced by ara‐C of human myeloid leukaemic cells

We investigated whether changes in iron metabolism and the transferrin receptor (TRF‐R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara‐C). Treatment with 100 n M ara‐C for 48 h reduced thymidine uptake and increased the surface expression of the TRF‐R on leukaemic blasts derived from 13/16 (81%) patients and on the HL‐60 and U‐937 cell lines. Whereas intracellular non‐haem iron was strongly depleted 24 h after ara‐C addition, TRF‐R up‐regulation and recovery of intracellular non‐haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara‐C and the iron chelator desferioxamine (DSF) on the growth of HL‐60 and U‐937 cells. We found that desferioxamine strongly potentiated the effects of ara‐C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara‐C and an iron chelator in terms of antileukaemic effects.

BRCA1 and BRCA2 mutations in central and southern Italian patients

Statement of findingsProtein truncation test (PTT) and single-strand conformation polymorphism (SSCP) assay were used to scan the BRCA1 and BRCA2 genes in 136 unrelated Italian breast/ovarian cancer patients. In the sample tested, BRCA1 and BRCA2 equally contributed to site-specific breast cancer patients who reported one to two breast cancer-affected first-/ second-degree relative(s) or who were diagnosed before age 40 years in the absence of a family history of breast/ovarian cancer. BRCA1 and BRCA2 mutations were mostly found in patients with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years and BRCA2 for tumours diagnosed after age 50 years. The BRCA1 and BRCA2 mutation spectrum was consistent with a lack of significant founder effects in the sample of patients studied.

p53 expression is decreased in primary breast carcinomas with microsatellite instability

Abstractp53 and p185 expression in primary breast cancer with microsatellite instability (MSI) is still largely unexplored. To investigate the relationship between these oncoproteins and the pathways of genomic instability, we examined 52 primary invasive breast cancers stratified by the presence and absence of MSI. We determined the status of eight microsatellite loci using radioactive and silver staining methods, and evaluated the immunohistochemical expression of p53 and p185 in a consecutive series of Italian cancer patients characterized by clinical-pathological and biological parameters. Nineteen cases (36.5%) were MSI-positive in at least two loci. p53 was expressed in 15 cases (28.8%) and p185 in eight (15.4%). MSI-positive tumors were inversely correlated with p53 expression ( p = 0.0007); in addition, the percent of p53-expressing cells decreased as the number of MSI-positive loci increased. MSI-positive tumors were correlated with a larger tumor size ( p = 0.04), lymph-node metastasis ( p = 0.001), and advanced clinical stage ( p = 0.0006). These data demonstrate the existence of two subsets of primary breast cancers: one characterized by MSI, the other by p53 expression. MSI-positive patients had a more advanced and/or aggressive disease.

Imaging tests in staging and surveillance of non-metastatic breast cancer: Changes in routine clinical practice and cost implications

Background:Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region.Methods:We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros.Results:We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays (‘routine tests’), and costs was unchanged. However, the number of CT, PET scans and MRI (‘new tests’)prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001).Conclusions:New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

Cancer prevalence in the city of Naples: Contribution of the GP database analyses to the cancer registries network

The Italian cancer registries network has not been sufficiently developed in the Southern regions. General practitioners (GPs) are knowledgeable about the prevalence, incidence and mortality for different types of cancer in their patient populations. The aim of this pilot study was to verify the feasibility and reliability of the characterization of cancer populations using GP databases in order to evaluate the impact of cancer in the general population of Naples. The characteristics of the cases studied have been collected by interview or electronic health record and recorded on paper or magnetic supports, appropriately conforming to the current privacy law. Databases are centralized, stored and codified on electronic data-sheets and periodically elaborated by the ‘Consorzio Nazionale delle Cooperative Mediche’ and ‘Federico II’ University. The present study was initiated on September 15, 2004. The analysed geographical area included the suburbs of ‘Stella’ and ‘San Carlo all’Arena’, situated in the historical center of Naples and corresponding to Health Care District 29 of the local health service. The analysis included 16,927 men and women (age range, 6–97 years) from the outpatient offices of 12 GPs who agreed to participate in the study. Results showed that the analysed population represents 16.3% of the general population residing in the area under study. We identified 342 (2%) patients with cancer, 143 (0.8%) of whom were men and 199 (1.2%) women (M/F ratio of 0.7). Of the 342 patients, 10 (5 men and 5 women) had a double cancer; thus, a total of 352 malignancies was characterized. Cancer prevalence was 2,020/100,000 inhabitants. This estimate is lower compared to the national prevalence (2,683/100,000 inhabitants) but higher compared to that in other southern Italian areas. Results, stratified by International Classification of Disease, ninth revision (ICD-IX), based on factors including gender and age, demonstrated that breast cancer, urogenital tumours and colorectal cancer are the most frequently occurring types of cancer identified among the inhabitants of Naples. Cancer prevalence in the historical center of Naples is in concordance with national estimates and projections and National Cancer Registries may be easily and accurately supported by GP medical databases.